Information Type

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

What is SB-728-T?

SB-728-T is categorized as an investigational gene therapy product. Gene therapy is an experimental technique that uses genes (short sections of genetic material) to treat or prevent disease. SB-728-T is a gene therapy product that involves modifying a gene in CD4 T cells, a type of immune cell that HIV attacks and destroys. By modifying the gene, SB-728-T can potentially prevent HIV from entering and infecting the CD4 T cells.3,4

One way that HIV enters and infects CD4 T cells is by attaching to a specific protein—called a CCR5 receptor—on the CD4 T cell surface. In some people, the CCR5 receptor is naturally genetically modified. People with this gene modification are more resistant to infection with the most common strain of HIV. SB-728-T treatment modifies the gene responsible for the CCR5 receptor and makes the CCR5 receptor non-functional. By modifying the CCR5 gene, SB-728-T potentially eliminates one way for the most common type of HIV to attach to and infect CD4 T cells.4,5

Production of SB-728-T begins by collecting CD4 T cells from an HIV-infected person. The cells are sent to a laboratory where they are genetically modified to make the CCR5 receptors non-functional. The cells are then stimulated to produce many more CD4 T cells with non-functional CCR5 receptors. Finally, the CD4 T cells are infused back into the person. This treatment may give HIV-infected individuals a population of CD4 T cells that are permanently resistant to HIV strains that use the CCR5 receptor for entering CD4 T cells. The modified CD4 T cells may also reproduce additional HIV-resistant CD4 T cells in the body.3-5

SB-728-T is being studied for its ability to restore immune function and as a possible strategy to cure HIV.3,4,6,7

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.8

Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.

Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.

Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.8

In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.8

In what phase of testing is SB-728-T?

What have recent studies shown about SB-728-T?

Below is information about two Phase I/II studies related to SB-728-T. The studies are known by their identification numbers: SB-728-0902 and SB-728-1101.

SB-728-0902
This study investigated the safety of SB-728-T and its effects on the immune system and HIV. All study participants were HIV-infected and had taken HIV medicines before entering the study (also called treatment-experienced participants). The study participants were assigned to five separate groups. Below is information about each of the groups.4,9

Groups 1 to 3: At the start of the study, all participants in Groups 1 to 3 had undetectable viral loads. (Viral load is a measure of the amount of HIV in the blood.) However, their CD4 counts were below desirable levels. (CD4 count is a measure of the number of CD4 T cells in the blood, which shows how well the immune system is working.) Participants in all three groups received a single intravenous (IV) infusion of SB-728-T, but in different amounts. Group 1 participants received the least amount of SB-728-T, and Group 3 participants received the greatest amount of SB-728-T. Participants continued to take their antiretroviral therapy (ART) throughout the study.4,10

Results for Groups 1 to 3 showed that SB-728-T treatment provided long-term increases in CD4 counts. Also, long-term improvement in CD4 counts appeared to be associated with reductions in participants’ latent HIV reservoirs. (Latent HIV reservoirs are resting CD4 cells or other cells that are infected with HIV but not actively producing HIV. Because the HIV “hidden” in the reservoirs is inactive, ART has no effect on it.) This study also identified certain immune factors that may have a role in determining how well a person responds to SB-728-T.10

Group 4: Participants in this group were not responding to their ART regimens (HIV was still at detectable levels in their blood). Results for this group are not yet available.4

Group 5: Before starting the study, Group 5 participants had normal CD4 counts and undetectable viral load levels. They also had one CCR5 gene that was already naturally modified; their other CCR5 gene was not modified. Participants received a single IV infusion of SB-728-T to modify the second CCR5 gene. Two months later, participants underwent a structured treatment interruption of ART. (A structured treatment interruption is a planned break from treatment, for example, ART. Structured interruption of ART is not recommended outside of clinical trials.) The structured interruption of ART was scheduled to last 16 weeks, but the exact length of the interruption depended on each participant’s viral load level and/or CD4 cell count.4,9

Results for Group 5 showed that three out of seven participants responded to SB-728-T treatment and had reductions in viral load during the structured interruption of ART. Two out of the three responders were able to control their viral load at or near undetectable levels while off ART. Out of the two participants who had undetectable viral loads while off ART, one had undetectable viral load levels for at least 14 weeks of the structured interruption. (The structured interruption of ART was still ongoing for this participant.) Three other participants, however, did not respond to SB-728-T treatment and either stopped the structured interruption early because of increased viral load or had no change in viral load at Week 16 of the structured interruption. One other participant had very little change in viral load at Week 16 of the structured interruption, but had not stopped the structured interruption of ART and was still being evaluated.6

SB-728-1101
This study looked at whether treating HIV-infected participants with IV cyclophosphamide (an FDA-approved drug for treating cancer) before they received SB-728-T could help to increase numbers of CD4 T cells in the body. Investigators also looked at how cyclophosphamide given before SB-728-T affected viral load levels during structured interruption of ART. All participants were treatment-experienced and had undetectable viral loads and normal CD4 counts before starting this study. The study compared three different strengths of cyclophosphamide given prior to SB-728-T treatment.7,11

In the SB-728-1101 study, cyclophosphamide helped to increase CD4 T cells in the body, including the SB-728-T-modified CD4 T cells. The higher doses of cyclophosphamide resulted in greater numbers of CD4 T cells in the body. In participants receiving the highest dose of cyclophosphamide, their levels of SB-728-T-modified CD4 T cells were comparable to levels that resulted in unmeasurable viral load during structured interruption of ART in people who had one CCR5 gene already naturally modified. Some participants in the SB-728-1101 study had viral load reductions during the structured interruption of ART.11

Additional Phase I and Phase I/II studies of SB-728-T have been completed.12,13

What side effects might SB-728-T cause?

In the SB-728-0902 study discussed under the previous question, SB-728-T was associated with some mild, reversible, infusion-related side effects.14

In a Phase I study, one serious side effect related to SB-728-T infusion was reported.12

Because SB-728-T is still being studied, information on possible side effects of the drug is not complete. As testing of SB-728-T continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying SB-728-T?

More information about SB-728-T-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

I am interested in participating in a clinical trial of SB-728-T. How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.8